chr1-45327386-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2
The NM_032756.4(HPDL):c.238A>G(p.Asn80Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HPDL
NM_032756.4 missense
NM_032756.4 missense
Scores
3
4
11
Clinical Significance
Conservation
PhyloP100: 6.05
Publications
0 publications found
Genes affected
HPDL (HGNC:28242): (4-hydroxyphenylpyruvate dioxygenase like) The protein encoded by this intronless gene localizes to mitochondria, where it may function as 4-hydroxyphenylpyruvate dioxygenase. Clinical studies have identified several bi-allelic variants in this gene that lower the level of the encoded protein and lead to a clinically variable form of pediatric-onset spastic movement disorder. [provided by RefSeq, Aug 2020]
HPDL Gene-Disease associations (from GenCC):
- neurodevelopmental disorder with progressive spasticity and brain white matter abnormalitiesInheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- Leigh syndromeInheritance: AR Classification: MODERATE Submitted by: ClinGen
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 21 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 0.93302 (below the threshold of 3.09). Trascript score misZ: -1.2259 (below the threshold of 3.09). GenCC associations: The gene is linked to Leigh syndrome, neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_032756.4. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1434804Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 712558
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1434804
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
712558
African (AFR)
AF:
AC:
0
AN:
33036
American (AMR)
AF:
AC:
0
AN:
42466
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25680
East Asian (EAS)
AF:
AC:
0
AN:
38600
South Asian (SAS)
AF:
AC:
0
AN:
83744
European-Finnish (FIN)
AF:
AC:
0
AN:
43162
Middle Eastern (MID)
AF:
AC:
0
AN:
5734
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1102920
Other (OTH)
AF:
AC:
0
AN:
59462
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Inborn genetic diseases (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MutPred
Loss of helix (P = 0.0626)
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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